In recent years, substantial advances have been made in cancer treatment modalities. Yet, within the last three decades, neither cancer incidence nor the cancer-induced mortality rate has changed. Available anti-cancer chemotherapeutics possess remarkably restricted effectiveness and often have severe adverse effects. Hence, the identification of novel pharmaceutical agents that do not exhibit these major disadvantages is imperative. Melatonin, an important endogenous molecule synthesized and secreted by the pineal gland, is a promising chemical agent that has been comprehensively assessed over the last decades for its anti-inflammatory and anti-cancer properties. Melatonin is reportedly a significant inhibitor of cancer initiation, progression, and metastasis. The anti-- cancer potential of melatonin is principally mediated by reversing the up-regulated amounts of different transcription factors, growth factors, inflammatory cytokines, protein kinases, and other oncogenic agents. Also, melatonin often has signifcant inhibitory effects on cancer cell proliferation through either promoting apoptosis or inducing cell cycle arrest. The current review provides an insight into melatonin-induced effects against various human cancers with a particular focus on the regulation of Wnt/β-catenin signaling pathway.